ArticleMolecular cell2019
Transient Hysteresis in CDK4/6 Activity Underlies Passage of the Restriction Point in G1.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
What it found
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Who cites it
70 citing papers in PubMed, 113 citations in OpenAlex.
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- Chromatin association promotes UBR5-mediated degradation of Rb.bioRxiv : the preprint server for biology · 2026Article
- Cyclin-E/A/CDK1/2 Kinetic Landscapes Drive Cell Cycle Phase-Specific Progression and Guide Cyclin-E Degradation Strategy.Journal of chemical information and modeling · 2026Article
- Protocol for iterative indirect immunofluorescence imaging of frozen mouse intestinal tissues.STAR protocols · 2026Article
- G1/S arrest: a key mechanism of cellular aging and replicative senescence.Biogerontology · 2026Review
- Identification and inhibition of the Cyclin D Rb-docking interface that drives cell division.bioRxiv : the preprint server for biology · 2026Article
- Article
- Intrinsic RB activation induces tumoral and stromal anti-tumor responses that limit triple-negative breast cancer.NPJ breast cancer · 2025Article
- Inactivation of CDK4/6, CDK2, and ERK in G1-phase triggers differentiation commitment.Communications biology · 2025Article
- Therapeutic benefits of maintaining CDK4/6 inhibitors and incorporating CDK2 inhibitors beyond progression in breast cancer.bioRxiv : the preprint server for biology · 2025Article
- Molecular and genetic evidence for the role of AMBRA1 in suppressing S-phase entry and tumorigenesis.iScience · 2025Article
- Mechanistic modeling of cell viability assays with in silico lineage tracing.PLoS computational biology · 2025Article
- E2F activity determines mitosis versus whole-genome duplication in G2-arrested cells.Nature communications · 2025Article
- Capturing CDKs in action: Live-cell biosensors pioneer the new frontiers in cell cycle research.Cell structure and function · 2025Review
- Mitochondrial priming and response to BH3 mimetics in "one-two punch" senogenic-senolytic strategies.Cell death discovery · 2025Article
- Cooperation between the Hippo and MAPK pathway activation drives acquired resistance to TEAD inhibition.Nature communications · 2025Article
- Article
- Combined treatment with CDK4/6, CDK2, and CXCR1/2 inhibitors effectively halts the growth of BRAF wild-type melanoma tumors.Frontiers in oncology · 2025Article
- A concise guide to fluorescent cell cycle reporters for live-cell imaging.Frontiers in cell and developmental biology · 2025Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Cells escape the need for mitogens at a restriction point several hours before entering S phase. The restriction point has been proposed to result from CDK4/6 initiating partial Rb phosphorylation to trigger a bistable switch whereby cyclin E-CDK2 and Rb mutually reinforce each other to induce Rb hyperphosphorylation. Here, using single-cell analysis, we unexpectedly found that cyclin E/A-CDK activity can only maintain Rb hyperphosphorylation starting at the onset of S phase and that CDK4/6 activity, but not cyclin E/A-CDK activity, is required to hyperphosphorylate Rb throughout G1 phase. Mitogen removal in G1 results in a gradual loss of CDK4/6 activity with a high likelihood of cells sustaining Rb hyperphosphorylation until S phase, at which point cyclin E/A-CDK activity takes over. Thus, it is short-term memory, or transient hysteresis, in CDK4/6 activity following mitogen removal that sustains Rb hyperphosphorylation, demonstrating a probabilistic rather than an irreversible molecular mechanism underlying the restriction point.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.